Fluidized bed adsorption has been recognized in the pharmaceutical industry as an attractive alternative to whole broth solvent extraction for isolating extracellular products from fermentation broths. Whole broth solvent extraction includes direct extraction with an immiscible solvent, followed by subsequent phase separation using centrifugal separators. There are several disadvantages associated with whole broth solvent extraction, i.e., the method requires costly centrifugal equipment and uses large volumes of solvent with associated requirements for large volume tanks and solvent recovery processing.
In a fluidized bed adsorption process a product or by-product is extracted directly from the fermentation broth onto an adsorbent in an upflow fluidized bed and can be subsequently eluted from the adsorbent particles. Fluidized bed adsorption avoids the problems of high equipment costs and high solvent use that are associated with the full broth extraction methods.
An adsorbent for use in fluidized bed adsorption of products from fermentation broths must have a higher terminal settling velocity than the broth solids, wherein terminal settling velocity means the upflow velocity at which particles will not remain in the column, so that the adsorbent particles remain in the column. The adsorbent particles must also exhibit a sufficiently high specific adsorptive capacity, i.e., grams of products adsorbed per gram adsorbent, for the product to be separated under the dynamic conditions in the fluidized bed to allow cost effective processing. Furthermore, since the products of the fermentation are to be used in pharmaceutical applications, it is highly desirable that the particles do not release any impurities during processing that might contaminate the product.
A brominated vinylaromatic adsorbent made by bromination of, e.g., a styrene-divinylbenzene copolymer, is disclosed in Japanese Patent No. 59089311. The adsorbent provides a specific surface area of at least 200 square meters per gram and has a bromine content of 3 to 20 weight percent. A brominated styrene-divinylbenzene copolymer has been used to separate immunomycin from a fermentation broth, see Gaillot, F. T., Gleason, C., Wilson, J. J. and Zwark, J., "Fluidized Bed Adsorption for Whole Broth Extraction", Biotechol. Prog. 6, 370-375 (1990).